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精神分裂症患者受体的基因多态性与抗精神病药物所致代谢功能障碍

Genetic Polymorphisms of Receptors and Antipsychotic-Induced Metabolic Dysfunction in Patients with Schizophrenia.

作者信息

Paderina Diana Z, Boiko Anastasiia S, Pozhidaev Ivan V, Bocharova Anna V, Mednova Irina A, Fedorenko Olga Yu, Kornetova Elena G, Loonen Anton J M, Semke Arkadiy V, Bokhan Nikolay A, Ivanova Svetlana A

机构信息

Mental Health Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634014 Tomsk, Russia.

Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634050 Tomsk, Russia.

出版信息

J Pers Med. 2021 Mar 5;11(3):181. doi: 10.3390/jpm11030181.

Abstract

BACKGROUND

Antipsychotic-induced metabolic syndrome (MetS) is a multifactorial disease with a genetic predisposition. Serotonin and its receptors are involved in antipsychotic-drug-induced metabolic disorders. The present study investigated the association of nine polymorphisms in the four 5-hydroxytryptamine receptor () genes , , , and and the gene encoding for the serotonin transporter with MetS in patients with schizophrenia.

METHODS

A set of nine single-nucleotide polymorphisms of genes of the serotonergic system was investigated in a population of 475 patients from several Siberian regions (Russia) with a clinical diagnosis of schizophrenia. Genotyping was performed and the results were analyzed using chi-square tests.

RESULTS

Polymorphic variant rs521018 () was associated with higher body mass index in patients receiving long-term antipsychotic therapy, but not with drug-induced metabolic syndrome. Rs1150226 () was also associated but did not meet Hardy-Weinberg equilibrium.

CONCLUSIONS

Our results indicate that allelic variants of genes may have consequences on metabolic parameters. MetS may have too complex a mechanistic background to be studied without dissecting the syndrome into its individual (causal) components.

摘要

背景

抗精神病药物所致代谢综合征(MetS)是一种具有遗传易感性的多因素疾病。血清素及其受体参与抗精神病药物所致的代谢紊乱。本研究调查了4个5-羟色胺受体(5-HT)基因(HTR1A、HTR2A、HTR2C和HTR7)以及血清素转运体(SLC6A4)编码基因中的9个多态性与精神分裂症患者MetS的相关性。

方法

在来自俄罗斯几个西伯利亚地区的475例临床诊断为精神分裂症的患者群体中,研究了一组血清素能系统基因的9个单核苷酸多态性。进行基因分型,并使用卡方检验分析结果。

结果

多态性变体rs521018(HTR2C)与接受长期抗精神病治疗的患者较高的体重指数相关,但与药物所致代谢综合征无关。Rs1150226(HTR2A)也有相关性,但不符合哈迪-温伯格平衡。

结论

我们的结果表明,5-HT基因的等位基因变体可能对代谢参数有影响。MetS的机制背景可能过于复杂,在不将该综合征分解为其各个(因果)组成部分的情况下难以进行研究。

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